Giving ovarian cancer cells a simple prod or squeeze to see how soft they are may be enough to provide an accurate indication of metastatic potential, scientists claim. A team at Georgia Institute of Technology has found that cell stiffness can distinguish ovarian cancer cells from non-malignant cancer cells, and also separate the more tumorigenic/invasive cancer cells form less tumorigenic/invasive types.
A link between the mechanical properties of cells and diseases such as cancer isn’t new, report Todd Sulchek, Ph.D., Wenwei Xu, Ph.D., and colleagues. Invasive tumor cells mechanically soften and change their adhesion to extracellular matrix, increasing their capacity to escape the primary tumor. Prior work has also indicated a correlation between cell deformity and cell malignancy. These changes are associated with alterations in cytoskeletal organization.
The Georgia team has now discovered that cell stiffness may be used to help identify ovarian cancer cells, and also predict their aggressiveness and metastatic potential. Their work, using atomic force microscopy mechanical measurements on single ovarian epithelial cells, showed that the force needed to indent a cell by prodding it with a probe was effectively much greater for immortalized ovarian surface epithelial (IOSE) cells than for those from the ovarian cancer HEY cell line, and the more aggressive HEY A8 cell lines. Effectively, the cancer cell lines were softer and more easily deformed when force was relative to IOSE using in vitro assays, and they found a significant inverse correlation between stiffness and migration and invasiveness, which are indicators of metastatic potential.
Subsequent gene expression profiling indicated that reduced cell stiffness in the cancer cells was associated with actin-mediated cytoskeletal remodeling, a finding that was supported by examination of the cytoskeletal structures of four different ovarian cancer cell lines in comparison with non-malignant IOSE cells.
The authors claim their findings suggest that mechanical stiffness may represent a useful biomarker in the development of accurate and non-invasive methods to evaluate the relative metastatic potential of ovarian and potentially other types of cancer cells. They report their studies in PLoS One, in a paper titled “Cell Stiffness Is a Biomarker of the Metastatic Potential of Ovarian Cancer Cells.”